Toxicity profile of bevacizumab in the UK Neurofibromatosis Type 2 cohort

Bevacizumab is considered an established part of the treatment strategies available for schwannomas in patients with Neurofibromatosis Type 2(NF2). In the UK, it is available through NHS National Specialized Commissioning to NF2 patients with a rapidly growing target schwannoma. Regrowth of the tumour on suspension of treatment is often observed resulting in prolonged periods of exposure to bevacizumab to control the disease. Hypertension and proteinuria are common events with bevacizumab use and there are concerns with regards to the long-term risks of prolonged treatment. Dosing, demographic and adverse event(CTCAE 4.03) data from the UK NF2 bevacizumab cohort are reviewed with particular consideration of renal and cardiovascular complications. Eighty patients (48 male:32female), median age 24.5 years (range 11-66years), were followed for a median of 32.7 months (range 12.0–60.2months). The most common adverse events were fatigue, hypertension and infection. A total of 19/80 patients (24%) had either a grade 2 or grade 3 hypertension event and 14/80 patients (17.5%) had proteinuria. Of 36 patients followed for 36 months, 78% were free from hypertension and 86% were free of proteinuria. Logistic regression modeling identified age and induction dosing regime to be predictors of development of hypertension with dose of 7.5mg/kg three weekly and age >30years having higher rates of hypertension. Proteinuria persisted in one of three patients after cessation of bevacizumab. One patient developed congestive heart failure and the details of this case are described. Further work is needed to determine optimal dosing regimes to limit toxicity without impacting on efficacy.

Labour and the free churches 1918-1939: radicalism, righteousness and religion

It is a commonplace that the labour movement was somehow nurtured within the witness for liberty of the Free Churches. Exploring this at a range of levels - including organisation, rhetoric, policies, electoral politics and people - this book demonstrates the extent to which this remained a reality into the inter-war years. The distinctive religious setting in which it emerged indeed helps to explain the differences between Labour and more Marxist counterparts on the Continent. It is shown here that this setting continued to influence Labour approaches towards welfare, nationalisation and industrial relations between the wars. In the process Labour also adopted some of the righteousness of tone of the Free Churches. This setting was, however, changing. Dropping their traditional suspicion of the State, Nonconformists instead increasingly invested it with religious values, turning it through its growing welfare functions into the provider of practical Christianity. This nationalisation of religion continues to shape British attitudes to the welfare state as well as imposing narrowly utilitarian and material tests of relevance upon the churches and other social institutions. The elevation of the State was not, however, intended as an end in itself. What mattered were the social and individual outcomes. Socialism, for those Free Churchmen and women who helped to shape Labour in the early twentieth century, was about improving society as much as systems.